Covid infection associated with a greater likelihood of Type 2 diabetes, according to review of patient records

Authors: Lenny Bernstein – March 21, 2022 The Washington Post

People who had covid-19 were at greater risk of developing Type 2 diabetes within a year than those who managed to avoid the coronavirus, according to a large review of patient records released Monday.

The finding is true even for people who had less severe or asymptomatic forms of coronavirus infection, though the chances of developing new-onset diabetes were greater as the severity of covid symptoms increased, according to researchers who reviewed the records of more than 181,000 Department of Veterans Affairs patients diagnosed with coronavirus infections between March 1, 2020, and Sept. 30, 2021.

Their data was compared to the medical records of more than 4.1 million VA patients who were not infected during the same period and another 4.28 million who received medical care from VA in 2018 and 2019. This kind of study cannot prove cause and effect, but it showed a strong association between the two diseases.

Overall, the researchers calculated that people diagnosed with covid-19, the disease caused by the coronavirus, were 46 percent more likely to develop Type 2 diabetes for the first time or be prescribed medication to control their blood sugar. The research was released Monday in the Lancet Diabetes & Endocrinology, a medical journal.

Put another way, 2 in 100 covid patients were more likely to develop Type 2 diabetes, a condition in which the pancreas makes insufficient amounts of the hormone insulin, leaving blood sugar levels poorly controlled. Type 2 diabetes can cause damage to kidneys, nerves, blood vessels and the heart, among its other effects.

The results have implications for the more than 471 million people known to have been infected during the pandemic, nearly 80 million of them in the United States, and especially for people suffering from long-haul covid.

“For the broader public, if you’ve had covid-19, you need to pay attention to your blood sugar,” said Ziyad Al-Aly, chief of research and development at VA St. Louis Health Care System, who led the review.

Previous smaller studies and physicians who have treated covid patients have noted an apparent increase in new diabetes diagnoses associated with coronavirus infection. But Al-Aly said his review was the largest consideration of the issue and looked at the greatest length of time after the acute phase of an infection — from 31 days after infection to a median of nearly one year per patient.

VA patients tend to be older than the general population, with more White people and males. But Al-Aly said the large numbers of people involved made him confident that his findings were applicable to the public.

“The risk was evident in all subgroups,” including women, racial minorities, younger people and people with different body mass indexes, he said.

More than 99 percent of the infected VA patients developed Type 2 diabetes, as opposed to Type 1, a condition in which insulin-producing cells in the pancreas stop producing the hormone entirely. Al-Aly speculated that the cells’ reduced efficiency may be caused by inflammation, produced either by the virus itself or the body’s response to it.

“Taken together,” the researchers wrote, “current evidence suggests that diabetes is a facet of the multifaceted long covid syndrome and that post-acute care strategies of people with covid-19 should include identification and management of diabetes.”

Hyperglycemia in Acute COVID-19 is Characterized by Adipose Tissue Dysfunction and Insulin Resistance

Authors: Reiterer MRajan MGómez-Banoy NLau JDGomez-Escobar LGGilani AAlvarez-Mulett SSholle ETChandar VBram YHoffman KRubio-Navarro AUhl SShukla APGoyal PtenOever BRAlonso LCSchwartz RESchenck EJSafford MM

Abstract 


COVID-19 has proven to be a metabolic disease resulting in adverse outcomes in individuals with diabetes or obesity. Patients infected with SARS-CoV-2 and hyperglycemia suffer from longer hospital stays, higher risk of developing acute respiratory distress syndrome (ARDS), and increased mortality compared to those who do not develop hyperglycemia. Nevertheless, the pathophysiological mechanism(s) of hyperglycemia in COVID-19 remains poorly characterized. Here we show that insulin resistance rather than pancreatic beta cell failure is the prevalent cause of hyperglycemia in COVID-19 patients with ARDS, independent of glucocorticoid treatment. A screen of protein hormones that regulate glucose homeostasis reveals that the insulin sensitizing adipokine adiponectin is reduced in hyperglycemic COVID-19 patients. Hamsters infected with SARS-CoV-2 also have diminished expression of adiponectin. Together these data suggest that adipose tissue dysfunction may be a driver of insulin resistance and adverse outcomes in acute COVID-19.

The deadly COVID-19 pandemic is underscored by the high morbidity and mortality rates seen in certain vulnerable populations, including patients with diabetes mellitus (DM), obesity, cardiovascular disease, and advanced age, with the latter associated with many chronic cardiometabolic diseases 14 . Hyperglycemia with or without a history of DM is a strong predictor of in-hospital adverse outcomes, portending a 7-fold higher mortality compared to patients with well-controlled blood glucose levels 5 . Hyperglycemia may be seen as a biomarker that predicts poor prognosis. A retrospective study that compared hyperglycemic patients that were treated with insulin against those who were not showed increased mortality in those receiving insulin 6 . However, it remains unclear whether insulin treatment is a surrogate for increased hyperglycemia and overall morbidity, or whether it is an actual causative factor for death. There is thus uncertainty regarding specific treatments for hyperglycemia in acute COVID-19 7 .

Despite our early recognition of the association between hyperglycemia and perilous outcomes, the pathophysiological mechanisms that underlie hyperglycemia in COVID-19 remain undefined 8,9 . Hypotheses have included a broad range of pathologies from direct infection of islets leading to beta cell failure (BCF) and to inflammation and glucocorticoids leading to insulin resistance (IR). Although COVID-19 is primarily a respiratory tract infection, SARS-CoV-2 is known to infect other cell types and often leads to extrapulmonary consequences 10,11 ACE2 and other entry receptors for SARS-CoV-2 can be expressed on pancreatic islet cells and endocrine cells differentiated from human pluripotent stem cells are permissive to infection 12 . Early reports of unexpected diabetic ketoacidosis (DKA) in COVID-19 patients fuelled concerns for a novel form of acute onset beta cell failure. For example, one case described a patient with new onset diabetic ketoacidosis (DKA) who was found to be autoantibody negative for type 1 DM (T1DM) but showed evidence of prior SARS-CoV-2 infection based on serology results, suggesting the possibility of pancreatic beta cell dysfunction or destruction as a result of COVID-19 13 . However, given the high rates of COVID-19 during this pandemic coupled with low background rates of new onset T1DM, the connection between these two events in this case could be “true, true, and unrelated.” Recent studies disagree on whether ACE2 is expressed on pancreatic beta cells or whether the SARS-CoV-2 virus is found in pancreatic beta cells of deceased individuals with COVID-19 1416 . Conversely, the well-known connection between obesity and insulin resistance might lead to impaired immunity and more severe SARS-CoV-2 infection 17 . In fact, population level studies have reported higher risk of complications in obese patients with COVID-19 1820 . Viral infection may lead to systemic insulin resistance and worsened hyperglycemia. In sum, despite much attention, the pathophysiology of hyperglycemia in COVID-19 remains unknown.

Dexamethasone substantially reduces mortality in patients with severe COVID-19 infection requiring oxygen or invasive mechanical ventilation 21 . Glucocorticoids can also provoke hyperglycemia by inducing insulin resistance and beta cell dysfunction. The widespread usage of dexamethasone in severe SARS-CoV-2 infection is sure to exacerbate both the incidence and severity of hyperglycemia in COVID-19.

For More Information: https://europepmc.org/article/PPR/PPR303316